Flavonoids in oral cancer prevention and therapy.

Oral cancer, representing all the malignancies arising in the oral cavity, is the eighth most diffused neoplasm worldwide. Despite therapeutic improvements, its survival rate has not changed significantly over the past few decades, with a 5-year survival rate slightly above 50%. In this context, a search for new therapeutic strategies is mandatory. Flavonoids, polyphenolic compounds derived from plants, have a broad spectrum of biological activities, including antioxidant and anticancer. They have been proved to counteract the growth of several types of cancer through multiple mechanisms including the inhibition of cell cycle progression, apoptosis induction, and the modulation of intracellular pathways. Because of their multiple biological activities and their safe toxicological profile, flavonoids have been studied widely in the last decade as potential leads for anticancer therapy. Several studies have reported different flavonoid effects according to cancer cell type. In the present review, therefore, we have evaluated the data available on the effect of flavonoids on oral cancer, with the aim of identifying the molecular mechanisms underlying their potential anticancer properties.

Myricetin and naringenin inhibit human squamous cell carcinoma proliferation and migration in vitro.

In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G0/G1 and a G2/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively. Western blot analysis showed that MYR induced a decrease of Cyclin D1 in SCC-25 and of Cyclin B1 in HaCaT cells, while NAR negatively modulated Cyclin D1 expression in SCC-25 cells. Wound-healing and cell invasion assays demonstrated that both the flavonoids were able to reduce motility on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC because they exert cytostatic effect by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as antimetastatic agents. Therefore, MYR and NAR appear as promising candidate as oral cancer chemopreventive agents.